Nicotinic receptors and Parkinson's disease

Accumulating evidence indicates that nicotinic receptors pray a role in bas al ganglia function. Furthermore, nicotine administration may be neuroprote ctive in animal models of nigrostriatal degeneration, while cigarette smoki ng is inversely correlated with Parkinson's disease. Because nicotinic rece ptors are decreased in Parkinson's disease, these observations may suggest that nicotinic agonists are beneficial in this disorder. We used two model systems to investigate this possibility. One involved non-human primates, w hich represent a good model because their neuroanatomical organization rese mbles that of man and nigrostriatal degeneration leads to biochemical and b ehavioral deficits similar to Parkinson's disease. To identify the subunits that comprise basal ganglia nicotinic receptors, we investigated alpha 4, alpha 6, alpha 7, beta 2, beta 3 and beta 4 transcript distribution in monk ey substantia nigra. All mRNAs were expressed with a selective alteration i n some transcripts after 1-methyl-4-phenyl-1,2,3,6-tetrahydropteridine (MPT P) induced nigrostriatal degeneration. As an approach to evaluate neuroprot ective effects of nicotine against nigral neuron damage, we used mesencepha lic neurons in culture, treated with a selective dopaminergic neurotoxin. T he results show that nicotine pretreatment protected against dopaminergic n igral neural degeneration. These data suggest that nicotinic receptor ligan ds may be useful in Parkinson's disease therapy. (C) 2000 Elsevier Science B.V. All rights reserved.